Recent findings that stem cells from a particular organ are capable of giving rise to mature tissues in other organs have changed our thinking about the role of stem cells in human disease and development. Bone marrow stem cells are among the most well characterized stem cells and they have been shown to be proficient in forming non-blood tissues. It is likely that bone marrow provides the cellular substrates for a many organs and that bone marrow derived precursors are recruited to areas of injury or wounds. There is evidence of this for the liver, heart and skeletal muscle. We have observed that bone marrow derived cells home to wounded skin, engraft to wounded skin and form skin structures. Virtual replacement of hair follicles and sebaceous glands has been documented and conversions of GFP+ marrow to cytokeratin positive keratinocytes demonstrated Understanding the dynamics of homing and recruitment of these bone marrow cells to the skin is a major goal of this project, along with studies on the capacity of marrow cells to facilitate healing of wounds. Understanding the mechanism behind such healing is also a goal, as is characterization of the origin of Hoechst "side-population" skin stem cells. Recent studies on the impact of whole marrow implantation on the healing of refractory skin ulcers in patients highlights the clinical potential of these approaches. The ability to utilize these adult stem cells may also allow us to avoid the use of unpredictable embryonic derived stem cells and may form the basis for all stem cell based treatments in the future.